Activation of NLRP3 Inflammasome Complexes by Beta-Tricalcium Phosphate Particles and Stimulation of Immune Cell Migration in vivo.

Beta-tricalcium phosphate (β-TCP) serves as a bone substitute in clinical practice because it is resorbable, biocompatible, osteointegrative, and osteoconductive. Particles of β-TCP are also inflammatory mediators although the mechanism of this function has not been fully elucidated. Regardless, the ability of β-TCP to stimulate the immune system might be useful for immunomodulation.

Effects of beta-tricalcium phosphate particles on primary cultured murine dendritic cells and macrophages.

Beta-tricalcium phosphate (β-TCP) is widely used for bone substitution in clinical practice. Particles of calcium phosphate ceramics including β-TCP act as an inflammation mediators, which is an unfavorable characteristic for a bone substituent or a prosthetic coating material. It is thought that the stimulatory effect of β-TCP on the immune system could be utilized as an immunomodulator.

Investigation of proNT/NMN secretion from small cell lung carcinoma cells using a mouse xenograft model.

Proneurotensin/neuromedin N (proNT/NMN), the precursor of neurotensin (NT) and neuromedin N (NMN), is produced by cancer tissues derived from the pancreas and colon. NT stimulates tumor growth and proliferation through its receptors; however, little is known about the precursor molecule in cancer tissues. We previously demonstrated that proNT/NMN is secreted from small cell lung carcinoma (SCLC) cell lines in serum-free conditioned medium, but not from non-small cell lung carcinoma (NSCLC) cell lines.

Fragrant environment with α-pinene decreases tumor growth in mice.

Stress is believed to be harmful to not only mental but also physical health. However, proving a link between stress and disease is difficult. A recent study reported that an environmental enrichment reduced cancer growth via the hypothalamic-pituitary-adrenal axis and leptin.

Flt3 ligand enhances anti-tumor effects of antibody therapeutics.

Fms-like tyrosine kinase 3 ligand ([Flt3 ligand], FL) stimulates proliferation and development of a wide range of hematopoietic cells including hematopoietic stem cells and myeloid and lymphoid progenitor cells. FL also has been shown to have anti-tumor effects in a variety of in vivo tumor models. In this study, the effect of FL against tumor growth was investigated in the COLO-205 human colon tumor xenograft model.

Antitumor activity of a novel small molecule STAT3 inhibitor against a human lymphoma cell line with high STAT3 activation.

Signal transducer and activator of transcription (STAT)3, a member of a family of DNA-binding molecules mediating numerous physiological and oncogenic signaling pathways, is a novel target in cancer cells which show high phosphorylation of STAT3. Recently, we identified a novel small-molecule inhibitor of STAT3 dimerization, STX-0119, as a cancer therapeutic. We investigated the mechanisms responsible for the antitumor activity in vitro and in vivo through numerous biochemical and biological assays.

Identification of a New Series of STAT3 Inhibitors by Virtual Screening.

The signal transducer and activator of transcription 3 (STAT3) is considered to be an attractive therapeutic target for oncology drug development. We identified a N-[2-(1,3,4-oxadiazolyl)]-4-quinolinecarboxamide derivative, STX-0119, as a novel STAT3 dimerization inhibitor by a virtual screen using a customized version of the DOCK4 program with the crystal structure of STAT3. In addition, we used in vitro cell-based assays such as the luciferase reporter gene assay and the fluorescence resonance energy transfer-based STAT3 dimerization assay.

Innate immunity and cancer therapy.

Classical cancer immunotherapy utilizes the immune response against microbial components, and a sequence of immune responses produce antitumor effects. The identification of mammalian Toll-like receptors (TLRs), receptors for microbial components, has shed light on antigen recognition by the innate immune system and provided a molecular basis for our understanding of the relationship between innate immunity and antitumor activity. However, accumulating evidence has revealed another important role of TLRs in maintaining tissue homeostasis and has also shown that tumor cells utilize this function to create favorable conditions for growth and survival, suggesting that TLR signaling acts as a double-edged sword in cancer therapy.